Two new mouse strains (BXSB and MRL/1) spontaneously develop a severe autoimmune disease characterized by LE cells, antibodies to DNA and immune complex glomerulonephritis. The BXSB males develop these features earlier than BXSB females. The MRL/1 mice also develop extensive lymphoproliferation. We propose to study autoimmunity in these strains as a problem of disordered immunologic regulation. We will test the hypothesis that sex hormones modulate autoimmunity by acting on thymic regulatory mechanisms. We will employ surgical, endocrinologic, histopathologic and immunologic methods developed in studies of NZB/NZW F1 mice. These experiments might lead to a better understanding of immunopathologic mechanisms and to new forms of therapy for autoimmune diseases.